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Reviewed, UniProtKB/Swiss-Prot Q03526 (ITK_MOUSE)

Last modified November 3, 2009. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Tyrosine-protein kinase ITK/TSK
    EC=2.7.10.2
Alternative name(s):
    T-cell-specific kinase
    IL-2-inducible T-cell kinase
    Kinase EMT
    Kinase TLK
Gene names
Name: Itk
Synonyms: Emt, Tlk, Tsk
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length625 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

May play a role in T-cell development, potentially in thymic selection.

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Ligation of CD2, TCR or CD28 induces activation and tyrosine phosphorylation of ITK. Interacts with THEMIS. Ref.5

Subcellular location

Cell membrane. Note: Localizes to cell surface receptors in the plasma membrane after stimulation with respective receptors (TCR, CD28, CD2) in T-cells.

Tissue specificity

Is detected in the thymus, lymph node and very faintly in the spleen, but is not detected in the liver, lung, kidney, heart, brain, intestine or testis. Expressed in T-lymphocytes and mast cells. It may also be expressed in natural killer cells.

Developmental stage

Is present in the fetal thymus as early as day 14 of gestation. The levels are 5- to 10-fold higher in thymocytes than in peripheral T-cells, and increase in the thymus during development from neonate to adult.

Induction

By interleukin-2.

Domain

The PH domain mediates targeting of ITK/TSK and is indispensible for the activation through TCR/CD3.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.

Contains 1 Btk-type zinc finger.

Contains 1 PH domain.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 625625Tyrosine-protein kinase ITK/TSK
PRO_0000088107

Regions

Domain4 – 117114PH
Domain177 – 23761SH3
Domain245 – 34399SH2
Domain368 – 620253Protein kinase
Zinc finger119 – 15537Btk-type
Nucleotide binding374 – 3829ATP By similarity

Sites

Active site4871Proton acceptor By similarity
Metal binding1271Zinc By similarity
Metal binding1381Zinc By similarity
Metal binding1391Zinc By similarity
Metal binding1491Zinc By similarity
Binding site3961ATP By similarity

Amino acid modifications

Modified residue1861Phosphotyrosine; by autocatalysis By similarity
Modified residue3011N6-acetyllysine By similarity
Modified residue5171Phosphotyrosine; by autocatalysis By similarity
Modified residue5701Phosphoserine By similarity

Experimental info

Sequence conflict82 – 876Missing Ref.2
Sequence conflict82 – 876Missing Ref.3
Sequence conflict82 – 876Missing Ref.4
Sequence conflict5351F → S in L10628. Ref.3
Sequence conflict5401Y → C in L10628. Ref.3

Secondary structure

1 ............................ 625
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Q03526-1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: F7A4A18A8A1AADDC

FASTA62572,292
        10         20         30         40         50         60 
MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI 

        70         80         90        100        110        120 
KCVEIVKSDI SIPCHYKYPF QTLVYLQVVH DNYLLYVFAP DCESRQRWVL TLKEETRNNN 

       130        140        150        160        170        180 
SLVSKYHPNF WMDGRWRCCS QLEKPAVGCA PYDPSKNASK KPLPPTPEDN RRSFQEPEET 

       190        200        210        220        230        240 
LVIALYDYQT NDPQELALRC DEEYYLLDSS EIHWWRVQDK NGHEGYAPSS YLVEKSPNNL 

       250        260        270        280        290        300 
ETYEWYNKSI SRDKAEKLLL DTGKEGAFMV RDSRTPGTYT VSVFTKAIIS ENPCIKHYHI 

       310        320        330        340        350        360 
KETNDSPKRY YVAEKYVFDS IPLLIQYHQY NGGGLVTRLR YPVCSWRQKA PVTAGLRYGK 

       370        380        390        400        410        420 
WVIQPSELTF VQEIGSGQFG LVHLGYWLNK DKVAIKTIQE GAMSEEDFIE EAEVMMKLSH 

       430        440        450        460        470        480 
PKLVQLYGVC LEQAPICLVF EFMEHGCLSD YLRSQRGLFA AETLLGMCLD VCEGMAYLEK 

       490        500        510        520        530        540 
ACVIHRDLAA RNCLVGENQV IKVSDFGMTR FVLDDQYTSS TGTKFPVKWA SPEVFSFSRY 

       550        560        570        580        590        600 
SSKSDVWSFG VLMWEVFSEG KIPYENRSNS EVVEDISTGF RLYKPRLASC HVYQIMNHCW 

       610        620 
KEKPEDRPPF SQLLSQLAEI AEAGL

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References

[1]"itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2."
Siliciano J.D., Morrow T.A., Desiderio S.V.
Proc. Natl. Acad. Sci. U.S.A. 89:11194-11198(1992) [PubMed: 1280821] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thymocyte.
[2]"Developmental regulation of a murine T-cell-specific tyrosine kinase gene, Tsk."
Heyeck S.D., Berg L.J.
Proc. Natl. Acad. Sci. U.S.A. 90:669-673(1993) [PubMed: 8421704] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thymocyte.
[3]"Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells."
Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A., Kato T., Inagaki Y., Kawakami T.
Biochem. Biophys. Res. Commun. 192:231-240(1993) [PubMed: 8476425] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CBA/J.
Tissue: Mast cell.
[4]Ogata M., Sawada M., Fujiwara H., Hamaoka T.
Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling."
Fu G., Vallee S., Rybakin V., McGuire M.V., Ampudia J., Brockmeyer C., Salek M., Fallen P.R., Hoerter J.A.H., Munshi A., Huang Y.H., Hu J., Fox H.S., Sauer K., Acuto O., Gascoigne N.R.J.
Nat. Immunol. 10:848-856(2009) [PubMed: 19597499] [Abstract]
Cited for: INTERACTION WITH THEMIS.
[6]"Regulatory intramolecular association in a tyrosine kinase of the Tec family."
Andreotti A.H., Bunnell S.C., Feng S., Berg L.J., Schreiber S.L.
Nature 385:93-97(1997) [PubMed: 8985255] [Abstract]
Cited for: STRUCTURE BY NMR OF 160-236.
[7]"CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line."
August A., Gibson S., Kawakami Y., Kawakami T., Mills G.B., Dupont B.
Proc. Natl. Acad. Sci. U.S.A. 91:9347-9351(1994) [PubMed: 7524075] [Abstract]
Cited for: CHARACTERIZATION.
[8]"CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK."
King P.D., Sadra A., Han A., Liu X.-R., Sunder-Plassmann R., Reinherz E.L., Dupont B.
Int. Immunol. 8:1707-1714(1996) [PubMed: 8943565] [Abstract]
Cited for: CHARACTERIZATION.
[9]"Emt/Itk associates with activated TCR complexes: role of the pleckstrin homology domain."
Ching K.A., Kawakami Y., Kawakami T., Tsoukas C.D.
J. Immunol. 163:6006-6013(1999) [PubMed: 10570288] [Abstract]
Cited for: CHARACTERIZATION.
+Additional computationally mapped references.

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Cross-references

Sequence databases

L00619 mRNA. Translation: AAA39337.1.
L05631 mRNA. Translation: AAA40518.1.
L10628 mRNA. No translation available.
D14042 mRNA. Translation: BAA03129.1.
IPIIPI00133425.
PIRA43030.
RefSeqNP_034713.2.
UniGeneMm.339927

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AWJNMR-A160-236[»]
1LUINMR-A238-344[»]
1LUKNMR-A238-344[»]
1LUMNMR-A238-344[»]
1LUNNMR-A238-344[»]
2ETZNMR-A238-344[»]
2EU0NMR-A238-344[»]
2K79NMR-A177-237[»]
B238-344[»]
2K7ANMR-A177-237[»]
B238-344[»]
2RN8NMR-A177-238[»]
2RNANMR-A177-238[»]
SMRQ03526. Positions 362-624.
ModBaseSearch...

Protein-protein interaction databases

IntActQ03526. 4 interactions.
STRINGQ03526.

PTM databases

PhosphoSiteQ03526.

Proteomic databases

PRIDEQ03526.

Genome annotation databases

EnsemblENSMUST00000020664; ENSMUSP00000020664; ENSMUSG00000020395; Mus musculus. [Genome view]
GeneID16428.
KEGGmmu:16428.

Organism-specific databases

CTD16428.
MGIMGI:96621. Itk.

Phylogenomic databases

HOGENOMQ03526.
HOVERGENQ03526.
OMAFEFMEHG.

Enzyme and pathway databases

BRENDA2.7.10.1. 244.
2.7.10.2. 244.

Gene expression databases

ArrayExpressQ03526.
BgeeQ03526.
CleanExMM_ITK.
GenevestigatorQ03526.
GermOnlineENSMUSG00000020395. Mus musculus.

Family and domain databases

InterProIPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR001562. Znf_Btk_motif.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.
PfamPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
PD000093. SH2. 1 hit.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio289653.
SOURCESearch...

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Entry information

Entry nameITK_MOUSE
AccessionPrimary (citable) accession number: Q03526
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 3, 2009
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents